Abstract
In Drosophila melanogaster, the axons of retinal photoreceptor cells extend to the first optic ganglion, the lamina, forming a topographic representation. Here we show that DWnt4, a secreted protein of the Wnt family, is the ventral cue for the lamina. In DWnt4 mutants, ventral retinal axons misprojected to the dorsal lamina. DWnt4 was normally expressed in the ventral half of the developing lamina and DWnt4 protein was detected along ventral retinal axons. Dfrizzled2 and dishevelled, respectively, encode a receptor and a signaling molecule required for Wnt signaling. Mutations in both genes caused DWnt4-like defects, and both genes were autonomously required in the retina, suggesting a direct role of DWnt4 in retinal axon guidance. In contrast, iroquois homeobox genes are the dorsal cues for the retina. Dorsal axons accumulated DWnt4 and misprojected to the ventral lamina in iroquois mutants; the phenotype was suppressed in iroquois Dfrizzled2 mutants, suggesting that iroquois may attenuate the competence of Dfrizzled2 to respond to DWnt4.
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05 January 2006
The PDF version of this article was corrected on 05 January 2006. Please see the PDF for the details.
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Acknowledgements
We thank T. Awasaki, B. Dickson and S. Kunes for critical comments on the manuscript; S. Cohen, N. Strausfeld, L. Ziparsky and members of the Tabata lab for helpful discussions; and Y. Maeyama for technical assistance. We are grateful to T. Akiyama, J. Axelrod, S. Campuzano, S. Cumberledge, E. Cohen, S. Cohen, B. Dickson, S. Hou, T. Kojima, E. Kuranaga, K. Matsuno, M. Miura, A. Nishida, R. Nusse, K. Saigo, A. Sato, G. Struhl, T. Suzuki, A. Tomlinson and E. Wilder for antibodies, fly strains and plasmids; the Bloomington Stock Center and the Drosophila Genetic Resource Center (Kyoto) for fly strains; and the Developmental Studies Hybridoma Bank for monoclonal antibodies. This work was supported by grants-in-aid from the Ministry of Education, Science, and Culture of Japan (M.S. and T.T.), by the Toray Science Foundation (T.T.) and by the Kato Memorial Bioscience Foundation (M.S.).
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Supplementary information
Supplementary Fig. 1
Retinotopic mapping at late third instar. (PDF 134 kb)
Supplementary Fig. 2
Outer- and inner-photoreceptor axons are affected in DWnt4 and iro backgrounds. (PDF 209 kb)
Supplementary Fig. 3
DWnt2 expression in the developing lamina. (PDF 100 kb)
Supplementary Fig. 4
R axon projections are regulated independently of the dorso-ventral patterning of the retinae. (PDF 414 kb)
Supplementary Fig. 5
Models. (PDF 150 kb)
Supplementary Fig. 6
DWnt4 expression in the glia, the retina and the early lamina. (PDF 174 kb)
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Sato, M., Umetsu, D., Murakami, S. et al. DWnt4 regulates the dorsoventral specificity of retinal projections in the Drosophila melanogaster visual system. Nat Neurosci 9, 67–75 (2006). https://doi.org/10.1038/nn1604
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DOI: https://doi.org/10.1038/nn1604
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